Abstract
The human 6q24 region is involved in growth and development, transient neonatal diabetes (TND), cancer, and metabolic dysfunction. To further characterize this region, the developmental status of DNA methylation and expression of Zac1 and Stx11 genes located within the mouse 10A1 region ortholog of human 6q24 were determined. In mice, imprinted Zac1 and Stx11 were highly expressed at the end of fetal development but downregulated at 4 and 11 weeks in brain, pancreas, and heart. Postnatal Zac1 downregulation was independent from promoter methylation of the expressed allele, suggesting the mediation of age-dependent chromatin remodeling. Stx11 nonpromoter CpG island was methylated de novo from E18 to 1 year with tissue-specific kinetics. The high conservation in vertebrates of Stx11 CpG2 is suggestive of an important regulatory function in age-related regional epigenetic state and/or chromatin configuration. Stx11 alleles were unequally expressed in F1 mice tissues, reflecting the influence of cis-regulatory factors on its expression. These data suggest the presence of a methylation domain and a coordinated gene expression pattern in multiple tissues. Methylation variation and allelic regulation of expression may underlie genetic diversity and contribute to disease susceptibility at the 6q24 locus in humans.
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Acknowledgments
We thank Prof. Claudine Junien for support and Prof. Andras Paldi for advice. We also thank Xavier Montagutelli, Institut Pasteur, Paris, France; Frank Letourneur, Institut Cochin de Génétique Moléculaire, Université René Descartes, Paris, France; the Centre National de la Recherche Scientifique (CNRS); and the Centre National d’Etude du Polymorphisme Humain (CEPH), Paris, France. Research funds were provided by grants from the Institut National de la Santé et de la Recherche Médicale (INSERM) and Association des Jeunes Diabètiques (AJD). GM holds a Ph.D. fellowship from the Ministère de l’Education Nationale de la Recherche et de la Technologie and Université Pierre et Marie Curie, Paris 6.
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Marcelin, G., Diatloff-Zito, C., Nicole, A. et al. Developmental methylation program and concerted expression of Stx11 in mouse tissues. Mamm Genome 20, 131–139 (2009). https://doi.org/10.1007/s00335-008-9162-5
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DOI: https://doi.org/10.1007/s00335-008-9162-5